Sequence variations of Epstein‐Barr virus‐encoded BARF1 gene in nasopharyngeal carcinomas and healthy donors from southern and northern China

Abstract

The BamHI A rightward frame 1 (BARF1) gene of the Epstein-Barr virus (EBV) is involved in carcinogenesis and immunomodulation of EBV-associated malignancies. The geographical distributions and the disease associations of BARF1 variants remain unclear. In the current study, the BARF1 variants in nasopharyngeal carcinoma (NPC) cases and healthy donors from southern and northern China, the NPC endemic and non-endemic areas, as well as in 153 sequenced EBV genomes from diseased and normal people from around the world, were determined and compared among areas and populations. Only 1 consistent coding change, V29A, and several consistent silent mutations were identified. Two BARF1 types (B95-8 and V29A) and 2 B95-8 subtypes (B95-8 and B95-8 ) were classified. For Chinese isolates, the B95-8 type was dominant in both southern and northern China, but the isolates from southern China showed a higher frequency of the B95-8 subtype than the isolates from northern China (76.0%, 38/50 NPC cases and 50.7%, 37/73 healthy donors vs 26.4%, 24/91 NPC cases and 7.6%, 6/79 healthy donors, P < .0001). Furthermore, the B95-8 subtype was more frequent in NPC cases than healthy donors in both southern China (P = .005) and northern China (P = .001). For EBV genomes, the B95-8 subtype was dominant in northern China, Europe, America, and Australia, while V29A was dominant in Africa. The B95-8 subtype was only identified in Asia and demonstrated high frequency (81.2%, 26/32) in genomes from NPC cases in southern China. These results further reveal conservation and possibly geographically spread variations of BARF1 and may also indicate the preference of EBV strains with the B95-8 subtype in NPC cases, without biological or pathogenic implications.

The Therapeutic Potential of Targeting BARF1 in EBV-Associated Malignancies

“…Although V29A is located within the first 54 residues of the amino-terminal transforming domain of BARF1, functional studies indicate that the V29A mutation does not influence cellular transformation [ 43 ]. Using a larger sample size ( n = 293), Liu et al found that only 16% (23/141) of NPC tumours obtained from southern and northern China harboured the V29A mutation [ 44 ]. Instead, a silent mutation at amino acid 14 was identified as the most frequent mutation in NPC tumours (44%, 62/141) compared to healthy controls (16%, 24/152).…”